Predictors of New-Onset Diabetes in Patients Treated With Atorvastatin: Results From 3 Large Randomized Clinical Trials

J Am Coll Cardiol. 2011 Apr 5;57(14):1535-45. doi: 10.1016/j.jacc.2010.10.047.

Abstract

Objectives: We sought to examine the incidence and clinical predictors of new-onset type 2 diabetes mellitus (T2DM) within 3 large randomized trials with atorvastatin.

Background: Statin therapy might modestly increase the risk of new-onset T2DM.

Methods: We used a standard definition of diabetes and excluded patients with prevalent diabetes at baseline. We identified baseline predictors of new-onset T2DM and compared the event rates in patients with and without new-onset T2DM.

Results: In the TNT (Treating to New Targets) trial, 351 of 3,798 patients randomized to 80 mg of atorvastatin and 308 of 3,797 randomized to 10 mg developed new-onset T2DM (9.24% vs. 8.11%, adjusted hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 0.94 to 1.29, p = 0.226). In the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial, 239 of 3,737 patients randomized to atorvastatin 80 mg/day and 208 of 3,724 patients randomized to simvastatin 20 mg/day developed new-onset T2DM (6.40% vs. 5.59%, adjusted HR: 1.19, 95% CI: 0.98 to 1.43, p = 0.072). In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial, new-onset T2DM developed in 166 of 1,905 patients randomized to atorvastatin 80 mg/day and in 115 of 1,898 patients in the placebo group (8.71% vs. 6.06%, adjusted HR: 1.37, 95% CI: 1.08 to 1.75, p = 0.011). In each of the 3 trials, baseline fasting blood glucose, body mass index, hypertension, and fasting triglycerides were independent predictors of new-onset T2DM. Across the 3 trials, major cardiovascular events occurred in 11.3% of patients with and 10.8% of patients without new-onset T2DM (adjusted HR: 1.02, 95% CI: 0.77 to 1.35, p = 0.69).

Conclusions: High-dose atorvastatin treatment compared with placebo in the SPARCL trial is associated with a slightly increased risk of new-onset T2DM. Baseline fasting glucose level and features of the metabolic syndrome are predictive of new-onset T2DM across the 3 trials.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Atorvastatin
  • Diabetes Mellitus, Type 2 / chemically induced*
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Female
  • Forecasting
  • Heptanoic Acids / adverse effects*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Incidence
  • Male
  • Middle Aged
  • Pyrroles / adverse effects*
  • Risk Factors

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Atorvastatin